March 11, 2014

Blood Test Identifies Those At Risk For Cognitive Decline, Alzheimer’s

A new study, led by Georgetown University, reveals that a blood test has been discovered and validated that can predict, with 90 percent accuracy, if a healthy person will develop mild cognitive impairment or Alzheimer's disease within three years.

The study, published in Nature Medicine, indicates the possibility of developing treatment strategies for Alzheimer's at an earlier stage. Therapy at these earlier stages would be more effective at slowing or preventing the onset of symptoms. The researchers say that their study is the first known report of blood-based biomarkers for preclinical Alzheimer's.

Ten lipids, or fats, that predict disease are identified in the blood by the new test, which could be ready for use in clinical trials in as little as two years. The researchers are hopeful for other diagnostic uses as well.

"Our novel blood test offers the potential to identify people at risk for progressive cognitive decline and can change how patients, their families and treating physicians plan for and manage the disorder," says Howard J. Federoff, MD, PhD, professor of neurology and executive vice president for health sciences at Georgetown University Medical Center.

To date, there is no cure or effective treatment for Alzheimer's disease. Approximately 35.6 million people suffer from the disease worldwide, and according to the World Health Organization (WHO), that number will double every 20 years. They predict 115.4 million sufferers by 2050.

There have been many efforts to develop drug therapies to slow or reverse the disease's progression, but according to Federoff, all have failed so far. He believes that one reason for this failure is that the drugs were evaluated too late in the disease process.

"The preclinical state of the disease offers a window of opportunity for timely disease-modifying intervention," Federoff says. "Biomarkers such as ours that define this asymptomatic period are critical for successful development and application of these therapeutics."

The researchers recruited 525 healthy participants aged 70 and older. The participants all gave blood samples at the beginning of the study and at various points during the study. Over the five-year study period, 74 participants met the criteria for either mild Alzheimer's disease (AD) or a condition known as amnestic mild cognitive impairment (aMCI), in which memory loss is prominent. Forty-six of this group were diagnosed upon enrollment in the study and 28 (called converters) developed aMCI or mild AD during the study.

During the study's third year, 53 participants who developed aMCI/AD (including 18 converters) and 53 cognitively normal matched controls were selected for the lipid biomarker discovery phase of the study. The lipids were not the initial focus of the study; instead, they were an outcome.

The researchers discovered a panel of 10 lipids that appear to reveal the breakdown of neural cell membranes in study participants who develop symptoms of cognitive impairment or AD. The team validated the panel using the remaining 21 aMCI/AD participants (including 10 converters), and 20 controls. To determine if the subjects could be characterized into the correct diagnostic categories based solely on the panel of 10 lipids identified in the discovery phase, the data was analyzed blind.

"The lipid panel was able to distinguish with 90 percent accuracy these two distinct groups: cognitively normal participants who would progress to MCI or AD within two to three years, and those who would remain normal in the near future," Federoff says.

The research team also investigated the possibility that the APOE4 gene, known to be a risk factor for developing AD, would contribute to accurate classifications of the groups. They found it was not a significant predictive factor, however.

"We consider our results a major step toward the commercialization of a preclinical disease biomarker test that could be useful for large-scale screening to identify at-risk individuals," Federoff says. "We're designing a clinical trial where we'll use this panel to identify people at high risk for Alzheimer's to test a therapeutic agent that might delay or prevent the emergence of the disease."